6qb8

Human CCT:mLST8 complexHuman CCT:mLST8 complex

6qb8, resolution 3.97Å

Structural highlights

6qb8 is a 16 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.97Å
Ligands:
Experimental data:	Check
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TCPB_HUMAN Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of proteins upon ATP hydrolysis (PubMed:25467444). The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance (PubMed:25467444). As part of the TRiC complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia (PubMed:20080638). The TRiC complex plays a role in the folding of actin and tubulin (Probable).^[1] ^[2]

Publication Abstract from PubMed

The mechanistic target of rapamycin (mTOR) kinase forms two multi-protein signaling complexes, mTORC1 and mTORC2, which are master regulators of cell growth, metabolism, survival and autophagy. Two of the subunits of these complexes are mLST8 and Raptor, beta-propeller proteins that stabilize the mTOR kinase and recruit substrates, respectively. Here we report that the eukaryotic chaperonin CCT plays a key role in mTORC assembly and signaling by folding both mLST8 and Raptor. A high resolution (4.0 A) cryo-EM structure of the human mLST8-CCT intermediate isolated directly from cells shows mLST8 in a near-native state bound to CCT deep within the folding chamber between the two CCT rings, and interacting mainly with the disordered N- and C-termini of specific CCT subunits of both rings. These findings describe a unique function of CCT in mTORC assembly and a distinct binding site in CCT for mLST8, far from those found for similar beta-propeller proteins.

Structural and functional analysis of the role of the chaperonin CCT in mTOR complex assembly.,Cuellar J, Ludlam WG, Tensmeyer NC, Aoba T, Dhavale M, Santiago C, Bueno-Carrasco MT, Mann MJ, Plimpton RL, Makaju A, Franklin S, Willardson BM, Valpuesta JM Nat Commun. 2019 Jun 28;10(1):2865. doi: 10.1038/s41467-019-10781-1. PMID:31253771^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Seo S, Baye LM, Schulz NP, Beck JS, Zhang Q, Slusarski DC, Sheffield VC. BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family chaperonins and mediate BBSome assembly. Proc Natl Acad Sci U S A. 2010 Jan 4. PMID:20080638 doi:http://dx.doi.org/0910268107
↑ Freund A, Zhong FL, Venteicher AS, Meng Z, Veenstra TD, Frydman J, Artandi SE. Proteostatic control of telomerase function through TRiC-mediated folding of TCAB1. Cell. 2014 Dec 4;159(6):1389-403. doi: 10.1016/j.cell.2014.10.059. Epub 2014 Nov , 20. PMID:25467444 doi:http://dx.doi.org/10.1016/j.cell.2014.10.059
↑ Cuellar J, Ludlam WG, Tensmeyer NC, Aoba T, Dhavale M, Santiago C, Bueno-Carrasco MT, Mann MJ, Plimpton RL, Makaju A, Franklin S, Willardson BM, Valpuesta JM. Structural and functional analysis of the role of the chaperonin CCT in mTOR complex assembly. Nat Commun. 2019 Jun 28;10(1):2865. doi: 10.1038/s41467-019-10781-1. PMID:31253771 doi:http://dx.doi.org/10.1038/s41467-019-10781-1

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OCA

[1] Seo S, Baye LM, Schulz NP, Beck JS, Zhang Q, Slusarski DC, Sheffield VC. BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family chaperonins and mediate BBSome assembly. Proc Natl Acad Sci U S A. 2010 Jan 4. PMID:20080638 doi:http://dx.doi.org/0910268107

[2] Freund A, Zhong FL, Venteicher AS, Meng Z, Veenstra TD, Frydman J, Artandi SE. Proteostatic control of telomerase function through TRiC-mediated folding of TCAB1. Cell. 2014 Dec 4;159(6):1389-403. doi: 10.1016/j.cell.2014.10.059. Epub 2014 Nov , 20. PMID:25467444 doi:http://dx.doi.org/10.1016/j.cell.2014.10.059

[3] Cuellar J, Ludlam WG, Tensmeyer NC, Aoba T, Dhavale M, Santiago C, Bueno-Carrasco MT, Mann MJ, Plimpton RL, Makaju A, Franklin S, Willardson BM, Valpuesta JM. Structural and functional analysis of the role of the chaperonin CCT in mTOR complex assembly. Nat Commun. 2019 Jun 28;10(1):2865. doi: 10.1038/s41467-019-10781-1. PMID:31253771 doi:http://dx.doi.org/10.1038/s41467-019-10781-1

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